This is a proposal to establish a National Resource for the development and application of Accelerator Mass Spectrometry (AMS) in broad-based biomedical research. The proposed Resource will make AMS available to biomedical researchers who have a need for accurately measuring very low levels of radioisotopes while exploring fundamental issues in biology. We will focus on 14C as it is extensively used in biomedical research and since AMS has unique detection capabilities for this isotope. Our short term goals are to expand present capabilities by developing biological and analytical methods for the routine use of AMS in biology, improving sample throughput to increase the number of studies that can be conduct, and to increase biomedical collaborator access to the technology. In the longer term, our goals are to expand the application areas for AMS in biology, export the methods and instrumentation required for its use and expand support for the use of AMS to the biosciences community. Throughout the tenure of this grant we will provide a resource to the research community that will include service to investigators familiar with AMS, training of new investigators in the technology and wide dissemination of the technology and its availability. Specific Aims for these goals are: (1) Develop new experimental methods necessary to utilize AMS in broad-based biological research. (2) Develop the sample preparation and analytical methods necessary to reduce handling, automate processes, and increase sample throughput so that a greater number of experiments can be accommodate with the existing technology. (3) Explore new spectrometer components allowing the direct interfacing of bioanalytical instrumentation to the spectrometer for simplified rapid on-line analysis. (4) Characterize and demonstrate a small AMS spectrometer capable of future placement in bioanalytical laboratories. This spectrometer will be developed during the course of this grant cycle and will replace the currently used larger 10 MV system.